Hydrogen-rich saline attenuates radiation-induced male germ cell loss in mice through reducing hydroxyl radicals

Abstract

Our recent studies suggest that H2 (hydrogen) has a potential as a novel radioprotector without known toxic side effects. The present study was designed to examine the underlying radioprotective mechanism of H2 and its protective role on irradiated germ cells. Produced by the Fenton reaction and radiolysis of H2O, hydroxyl radicals (•OH) were identified as the free radical species that were reduced by H2. We used a H2 microelectrode to dynamically detect H2 concentration in vivo, and found H2 significantly reduced in situ fluorescence intensity of hydroxyphenyl fluorescein; however, as we treated the mice with H2 after irradiation, the decrease is not significant. We found that pre-treatment of H2 to IR (ionizing radiation) significantly suppressed the reaction of •OH and the cellular macromolecules which caused lipid peroxidation, protein carbonyl and oxidatively damaged DNA. The radioprotective effect of H2 on male germ cells was supported by ameliorated apoptotic findings examined by morphological changes and TUNEL (terminal deoxynucleotidyltransferase-mediated dUTP nick-end labelling) in testicular tissue, and by preserved viability of stem spermatogonia examined for testicular histological parameters, daily sperm production and sperm quality; we used WR-2721 [S-2-(3-aminopropylamino)ethyl phosphorothioic acid] as a reference compound. Our results represent the first in vivo evidence in support of a radioprotective role of H2 by neutralizing •OH in irradiated tissue with no side effects.

Hydrogen as a New Class of Radioprotective Agent

“…Recent basic and clinical research revealed that hydrogen is an important physiological regulatory factor with antioxidant, anti-inflammatory and anti-apoptotic protective effects on cells and organs 35-40. Hydrogen was also demonstrated has radioprotective effects on cultured cells and mice 11-16, 41 (Figure 2). H 2 exert antioxidative effects with few toxic side effects.…”

Molecular hydrogen protects against oxidative stress-induced SH-SY5Y neuroblastoma cell death through the process of mitohormesis

“…We also confirmed that the dissolved H 2 reduces ·OH produced by the Fenton reaction, ultraviolet irradiation, or sonication in vitro , as judged by the fluorescence of 3'- p -(hydroxyphenyl) fluorescein and the electron spin resonance spectrum of 5,5-dimethyl-1-pyrroline N -oxide [4–6]. The reduction of ·OH by H 2 was further observed in cultured cells, male germ cells in mouse, and retinas in rat [4, 7, 8]. These observations indicate that a sufficient amount of H 2 can efficiently moderate oxidative damage induced by ·OH.…”

Hydrogen-rich saline protects immunocytes from radiation-induced apoptosis

“…H 2 is produced by bacteria in the body and then released into the circulation [21], and the reaction between H 2 and •OH produces water [22], indicating that low concentration H 2 could be safe for human health. Therefore dissolving it in PBS, physiological saline or medium would provide a convenient method of application.…”